Intracranial Activity of AZD9291 (TAGRISSO) in Advanced EGFRm NSCLC Patients With Asymptomatic Brain Metastases

Inclusion Criteria

• •1. Provision of informed consent prior to any study specific procedures
• •2. Male or female, aged at least 18 years.
• •3. Group A: treatment-naïve advanced NSCLC with an sensitizing EGFR mutation.
• •* Patients who received adjuvant/neo-adjuvant chemotherapy/chest irradiation/palliative irradiation (other than brain) allowed.
• •* Exon 19 deletion, L858R, T790M and uncommon sensitizing EGFR mutations in treatment-naïve patients are allowed.
• •Or
• •Group B: patients advanced NSCLC previously treated with 1st/2nd-generation EGFR TKIs (either gefitinib. erlotinib or afatinib) in whom T790M was diagnosed in the tumor specimen or ctDNA after testing it following the most recent disease progression.
• •* No restriction regarding the number of prior EGFR TKIs or cytotoxic chemotherapy lines of treatment is applied.
• •* Group C: patients advanced NSCLC previously treated with 1st/2nd generation EGFR TKIs (either gefitinib. erlotinib or afatinib) who progressed unrelated to T790M (T790M-). No restriction regarding the number of prior EGFR TKIs or cytotoxic chemotherapy lines of treatment is applied.
• •4. Asymptomatic untreated brain metastases (previously SRS more than 6 month).
• •5. Measurable intracranial disease by mRECIST criteria (less or equal to 5 mm).
• •6. Normal hematologic, renal and liver function:
• •Absolute neutrophil count above 1500/mm3, platelets above 100,000/mm3, hemoglobin above 9 g/dL; createnine concentration is less or equal to 1.5 mg/dL, or createnine clearance less then 60 ml/min. Total bilirubin less or equal to 1.5 mg/dL, ALT+ AST levels 5 times above the upper normal limit.
• •7. World Health Organization (WHO) performance status 0-2.
• •8. Patients must have a life expectancy ≥ 12 weeks.
• •9. Females should be using adequate contraceptive measures, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• •* Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
• •* Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution
• •* Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation
• •10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• •11. All patients with reproductive potential must agree to use barrier contraception methods while receiving the study treatment.
• •12. Patients has the ability to read and write and use the electronic devices.
• •13. At least one lesion (measurable and/or non-measurable) that can be accurately assessed by CT/MRI at baseline and follow up visits.